1. Field of the Invention
The present invention relates generally to the fields of endocrinology and pharmacology. More specifically, the present invention relates to the use of dehydroepiandrosterone to treat primary adrenal insufficiency and Addison's disease.
2. Description of the Related Art
In 1855, Thomas Addison described the clinical features, natural history and autopsy findings of the disease that now bears his name. Addison's disease is a rare condition of primary adrenal insufficiency resulting from destruction of the adrenal gland and is caused by a variety of disorders, the most common of which is "autoimmune in origin", Oelkers, W. Adrenal Insufficiency. N Eng J Med 1996 335:1206-1212. The incidence of the disease is 40-60 cases per million young adults with a female/male ratio of 10 to 1 Mason, A. S., et al. Epidemiological and Clinical Picture of Addison's Disease. Lancet 1968, 2:744-747. In this condition, all three zones of the adrenal cortex are affected by the destructive processes (3,4). Consequently inadequate adrenal secretion of glucocorticoid, mineralocorticoid and androgen precursors such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DS) occurs, Yamaji, T. et al. Plasma DHEAS In Normal And Pathological Conditions. J. Clin Endocrinol Metab 1969, 29: 273 and Urban, M. et al., Androgens In Pubertal Males With Addison's Disease. J Clin Endocrinal Metab 1980 51:925-929.
The onset of manifestation is usually gradual, going first through a stage of partial adrenal deficiency and followed sometime later by the overt cortisol deficiency which results clinically in nausea and vomiting, weight loss and anorexia. It is also associated with fever and hypoglycemia. In cases where mineralocorticoid production is decreased, hyponatremia and hyperkalemia occur. Hyperpigmentation of mucosa and skin occurs due to excessive pituitary ACTH secretion (secondary to the lack of cortisol feedback) and the associated overproduction of MSH-like peptides with pigmenting effect of the skin and mucus membranes, Mains, R. E., et al., Synthesis And Secretion Of Corticotrophins, Melantrophins And Endorphins By Rat Immediate Pituitary Cells. J Biol Chem 1979, 254:7885-7894 and Carter, R. J., et al., Melanotrophin Potentiating Factor Is The C-Terminal Tetrapeptide Of Human .beta.-Lipotrophin.
Nature 1979, 279:34-75. Not infrequently the autoimmune processes also involve other endocrine glands and hypothyroidism and premature ovarian failure may be part of the clinical manifestation, Oelkers, W. Adrenal Insufficiency. N Eng J Med 1996, 335:1206-1212, Irvine, W. J., et al. Adrenocortical Insufficiency. Clin Endocrinol Metab Metab 1972, 1:549-594, Mason, A. S., et al. Epidemiological And Clinical Picture Of Addison's Disease. Lancet 1968, 2:744-747, Eisenbarth, G. S., et al. The Immunoendocrinopathy Syndromes. In: Wilson, J. D., Foster, D. W., Ed. Williams Textbook Of Endocrinology, Saunders, Philadelphia, 1992: 1555-1566, Nerup, J. Addison's Disease. Clinical Studies. A report of 108 cases. Acta Endocrinol 1974, 76: 27-141, Spinner, M. W., et al. Clinical And Genetic Heterogeneity In Idiopathic Addison's Disease And Autoimmune Hypoparathyroidism. J Clin Endocrinal Metab 1968, 28: 795-804.
While replacements of glucocorticoids and mineralocorticoids are standard management of Addison's disease, no attempts to replace adrenal androgen have been properly made to date. Oelkers, W., Adrenal Insufficiency, N Eng J Med, 1996, 335:1206-1212. Patients with Addison's disease frequently complain of fatigue, loss of pubic and axillary hair, decreased libido and muscle weakness in spite of adequate replacement of adrenal corticoids. Burke, C. W. Primary Adrenocortical Failure. In: Grossman A. Clinical Endocrinology, Ed. Oxford: Blackwell: 1992:393-404, Zelissen P. M., et al. Effect Of Glucocorticoid Replacement Therapy On Bone Mineral Density In Patients With Addison's Disease. Ann Int Med, 1994, 120:207-210 and Riedel, M., et al. Quality Of Life In Patients With Addison's Disease: Effects Of Different Cortisol Replacement Modes. Exper Clin Endocrinol, 1993, 101:106-111.
The prior art is deficient in the lack of effective means of treating Addison's disease and primary or secondary adrenal insufficiency. The present invention fulfills this longstanding need and desire in the art.